This is interesting and a novel study. Did you look at whether any protective or possibly protective mutations in ABCA1 or ABCA7 where associated with the more resilient E4 carriers , esp homozygotes? Searchable RS sequences would be immediately useful - eg rs2230805 (ABCA1 L158L)
Great question. We did not examine ABCA1 or ABCA7 variants in this analysis, but this is an important next step. The variants you mention have shown potentially protective associations in some studies, although the evidence is not consistent. It would be particularly interesting to determine whether these variants help explain why some APOE4 homozygotes remain cognitively resilient, and whether their effects are related to improved APOE lipidation. Our study included only 26 APOE4 homozygotes, so answering this question will require larger cohorts with genetic and functional lipid measurements. Thank you for highlighting these specific variants.
This is interesting and a novel study. Did you look at whether any protective or possibly protective mutations in ABCA1 or ABCA7 where associated with the more resilient E4 carriers , esp homozygotes? Searchable RS sequences would be immediately useful - eg rs2230805 (ABCA1 L158L)
- rs2230806 (ABCA1 R219K)
- rs72973581 (ABCA7 G215S) ?
Great question. We did not examine ABCA1 or ABCA7 variants in this analysis, but this is an important next step. The variants you mention have shown potentially protective associations in some studies, although the evidence is not consistent. It would be particularly interesting to determine whether these variants help explain why some APOE4 homozygotes remain cognitively resilient, and whether their effects are related to improved APOE lipidation. Our study included only 26 APOE4 homozygotes, so answering this question will require larger cohorts with genetic and functional lipid measurements. Thank you for highlighting these specific variants.